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Solid Tumour Section
Mini Review
Uterus: Carcinoma of the cervix
Niels B Atkin
Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex, UK (NBA)
Published in Atlas Database: May 2000
Online updated version : http://AtlasGeneticsOncology.org/Tumors/CervixUteriID5046.html
DOI: 10.4267/2042/37649
This article is an update of : Atkin NB. Carcinoma of the Cervix Uteri. Atlas Genet Cytogenet Oncol Haematol 1999;3(3):162-163.
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2000 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Carcinomas are staged as follows:
IA: early invasive, not grossly visible;
IB: usually grossly visible, but confined to the cervix;
IIA: spread to the upper two thirds of the vagina only;
IIB: lateral extension into the parametrium;
IIIA: involvement of the lowest third of the vagina;
IIIB: involvement of the pelvic side wall or
hydronephrosis;
IVA: bladder or rectal involvement;
IVB: distant metastasis.
Classification
Note
- Squamous cell carcinoma (80%);
- Adenocarcinoma (10%);
- Adenoacanthoma (10%).
Clinics and pathology
Disease
Carcinoma of the cervix uteri; usually arises in the
transitional zone between squamous and columnar cell
epithelium.
Treatment
Etiology
Evolution
Infection with high-risk forms of the human
papillomavirus (HPV) is established as the major
factor: a secondary factor is cigarette smoking; recent
evidence suggests that a polymorphic variant of the
tumour suppressor P53 (p53Arg) may represent a risk
factor for cervical carcinogenesis.
Preinvasive stage, detectable by cervical cytology,
shows a peak incidence between 25 and 40 years; that
of invasive cancer is 40-50 years, thus indicating that
the preinvasive usually progresses to the invasive stage
over a very prolonged period.
Radiotherapy and/or surgery; late stages: radiotherapy
supplemented by chemotherapy (e.g. cisplatin).
Prognosis
Epidemiology
Preinvasive lesions are curable by local removal; stage
I and early IIA cases may expect 80-90% five year
survival; later cases show survival rates of 65-20% or
less.
Over 470,000 new cases are diagnosed annually
worldwide.
Clinics
Haematuria.
Cytogenetics
Cytology
Note
Polyploidisation, with modes in the triploid region or
above, is common, particularly in the preinvasive phase
where it may be linked to the frequent spindle
anomalies that result, for instance, in the "three group"
metaphases seen in histological sections and
chromosome preparations; structural changes are
commonest in chromosomes 1, 3, 5, 11 and 17 where,
Cervical smears confirm the diagnosis of carcinoma or
may reveal the presence of the disease in its
preinvasive (preclinical) stage.
Pathology
Three grades of preinvasive carcinoma-in-situ (CIN)
are recognised: I (which usually undergoes spontaneous
resolution), II and III;
Atlas Genet Cytogenet Oncol Haematol. 2000; 4(3)
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Uterus: Carcinoma of the cervix
Atkin NB
except in chromosome 5, they most often result in
short-arm deletions.
from patients with CIN II or III strongly suggests that
progression to carcinoma will occur.
Cytogenetics Morphological
References
Chromosome 1: changes may also result in the
acquisition of additional long-arm material (as is
common in other types of carcinoma), e.g. in the form
of a 1q isochromosome.
Chromosome 3: additional material on 3q has been
shown by comparative genomic hybridization (CGH) in
90% of carcinomas and this gain may occur at the point
of transition from severe dysplasia to invasive
carcinoma; recent studies suggest involvement of the
hTR gene which encodes the RNA component of
telomerase; loss of heterozygosity (LOH) studies
indicate that there are two regions on 3p where tumour
suppressor genes may be situated: at 3pl4.2 (FHIT
gene) and at 3q21, gene not yet identified.
Chromosome 4: LOH studies suggest that at least two
genes are important, at 4p16 and 4q21-35.
Chromosome 5: an i(5p), often in two or more copies,
is a frequent finding in cervical carcinomas, and this is
consistent with CGH studies which show amplification
of 5p, particularly in advanced stages.
Chromosome 6: LOH studies show a high frequency of
loss in the region 6p21.3-p25.
Chromosome 11: possible gene loss on both
chromosome arms are suggested by LOH studies, at
11p15 and 11q23; identities of the genes have yet to be
determined.
Chromosome 17: G-banding and LOH studies have
shown the nonrandom loss of 17q, where the P53 gene
is situated (at 17p13.3); mutations or loss of this gene
are, however, relatively infrequent compared with other
types of tumour, perhaps because there is instead
interaction between p53 protein and the HPV E6 viral
gene in most carcinomas of the cervix; indeed, p53
appears to be more frequently mutated in HPVnegative tumours.
Role of HPV: types 16 and 18 are associated with about
70% of cervical carcinomas (other high-risk types
include 31, 33, 35, 39, 51, 52, and 56); these high-risk
types are often demonstrable in the moderate and
severe stages of preinvasive malignancy (CIN II and
III); in these lesions they are commonly situated
extrachromosomally while in carcinomas they are
integrated into chromosomes at random locations,
where they undergo disruption of the HPV E2 viral
transcriptional regulatory protein; integration may
thereby provide a selective advantage resulting in
uncontrolled cellular proliferation leading to
aneuploidy; it has recently been shown that a single
finding of HPV DNA in a Pap smear from healthy
women confers an increased risk of future invasive
carcinoma that is positive for the same type of virus.
Another recent study suggests that integration of highrisk HPV DNA in cervical swabs or tissue removed
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Atlas Genet Cytogenet Oncol Haematol. 2000; 4(3)
This article should be referenced as such:
Atkin NB. Uterus: Carcinoma of the cervix. Atlas Genet
Cytogenet Oncol Haematol. 2000; 4(3):142-144.
144